Activation of Ca2+/calmodulin-dependent protein kinase II and protein kinase C by glutamate in cultured rat hippocampal neurons

J Biol Chem. 1992 Nov 5;267(31):22527-33.


In cultured rat hippocampal neurons, glutamate elevated the Ca(2+)-independent activity of Ca2+/calmodulin-dependent protein kinase II (CaM kinase II) through autophosphorylation when the neurons were incubated in Mg(2+)-free buffer, and this response was blocked by specific antagonists of the N-methyl-D-aspartate (NMDA) receptor. In addition, glutamate stimulated the transient translocation of protein kinase C (PKC) from the cytosol to the membrane fraction. This effect was not blocked by NMDA receptor antagonists but was partially blocked by DL-2-amino-3-phosphonopropionate. Quisqualate or trans-1-amoinocyclopentane-trans1,3-dicarboxylate produced a similar effect on the translocation of PKC. In the experiments with 32P-labeled cells, the phosphorylation of microtuble-associated protein 2 and synapsin I, as well as autophosphorylation of CaM kinase II, were found to be stimulated by exposure to glutamate. These results suggest that glutamate can activate CaM kinase II through the ionotropic NMDA receptor, which in turn increases the phosphorylation of microtuble-associated protein 2 and synapsin I. PKC was activated through the metabotropic glutamate receptor in the hippocampal neurons.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Calcium / physiology
  • Calcium-Calmodulin-Dependent Protein Kinases
  • Cells, Cultured
  • Enzyme Activation / drug effects
  • Fluorescent Antibody Technique
  • Glutamates / pharmacology*
  • Glutamic Acid
  • Hippocampus / enzymology*
  • In Vitro Techniques
  • Membrane Potentials
  • Microtubule-Associated Proteins / metabolism
  • Nerve Tissue Proteins / metabolism
  • Neurons / enzymology
  • Phosphorylation
  • Protein Kinase C / metabolism*
  • Protein Kinases / metabolism*
  • Rats
  • Receptors, Glutamate / physiology*
  • Signal Transduction
  • Synapsins / metabolism


  • Glutamates
  • Microtubule-Associated Proteins
  • Nerve Tissue Proteins
  • Receptors, Glutamate
  • Synapsins
  • Glutamic Acid
  • Protein Kinases
  • Protein Kinase C
  • Calcium-Calmodulin-Dependent Protein Kinases
  • Calcium